4EC2

Crystal structure of trimeric frataxin from the yeast Saccharomyces cerevisiae, complexed with ferrous

Summary for 4EC2

• Entry DOI: 10.2210/pdb4ec2/pdb
• Related: 2FQL 3OEQ 3OER
• Descriptor: Frataxin homolog, mitochondrial, FE (II) ION (2 entities in total)
• Functional Keywords: alpha/beta sandwich, metallochaperone, iron-storage, transport protein
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Mitochondrion matrix : Q07540
• Total number of polymer chains: 1
• Total formula weight: 13727.03

Authors

Soderberg, C.A.G.,Rajan, S.,Gakh, O.,Isaya, G.,Al-Karadaghi, S. (deposition date: 2012-03-26, release date: 2013-01-30, Last modification date: 2023-09-13)

Primary citation

Soderberg, C.A.,Rajan, S.,Shkumatov, A.V.,Gakh, O.,Schaefer, S.,Ahlgren, E.C.,Svergun, D.I.,Isaya, G.,Al-Karadaghi, S.
The molecular basis of iron-induced oligomerization of frataxin and the role of the ferroxidation reaction in oligomerization.
J.Biol.Chem., 288:8156-8167, 2013

PubMed Abstract: The role of the mitochondrial protein frataxin in iron storage and detoxification, iron delivery to iron-sulfur cluster biosynthesis, heme biosynthesis, and aconitase repair has been extensively studied during the last decade. However, still no general consensus exists on the details of the mechanism of frataxin function and oligomerization. Here, using small-angle x-ray scattering and x-ray crystallography, we describe the solution structure of the oligomers formed during the iron-dependent assembly of yeast (Yfh1) and Escherichia coli (CyaY) frataxin. At an iron-to-protein ratio of 2, the initially monomeric Yfh1 is converted to a trimeric form in solution. The trimer in turn serves as the assembly unit for higher order oligomers induced at higher iron-to-protein ratios. The x-ray crystallographic structure obtained from iron-soaked crystals demonstrates that iron binds at the trimer-trimer interaction sites, presumably contributing to oligomer stabilization. For the ferroxidation-deficient D79A/D82A variant of Yfh1, iron-dependent oligomerization may still take place, although >50% of the protein is found in the monomeric state at the highest iron-to-protein ratio used. This demonstrates that the ferroxidation reaction controls frataxin assembly and presumably the iron chaperone function of frataxin and its interactions with target proteins. For E. coli CyaY, the assembly unit of higher order oligomers is a tetramer, which could be an effect of the much shorter N-terminal region of this protein. The results show that understanding of the mechanistic features of frataxin function requires detailed knowledge of the interplay between the ferroxidation reaction, iron-induced oligomerization, and the structure of oligomers formed during assembly.

PubMed: 23344952
DOI: 10.1074/jbc.M112.442285

Experimental method

X-RAY DIFFRACTION (3.002 Å)